| Co-Investigator(Kenkyū-buntansha) |
YURI Kazunari Kochi University, Department of Neurobiology and Anatomy, MD., PhD. Professor (10220534)
OSAKO Yoji Kochi University, Department of Neurobiology and Anatomy, PhD. Assistant Professor (40335922)
ADACHI Kiyomi Kochi University, Department of Neurobiology and Anatomy, PhD. Assistant Professor (60335932)
HOSOKAWA Takatoshi Kochi University, Department of Pediatrics, MD., PhD. Assistant Professor (10380312)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Our aim is the development of novel therapy and diagnostic method for developmental disorders based on the molecular mechanism of the disease. In this study, we analyzed 1) the behavioral phonotype of mice lacking a mental retardation gene, motopsin (prss12), and 2) spatio-temporal localization of a motopsin-interacting protein, SEZ6.
Motopsin-deficient mice showed moderately impaired spatial memory. A social memory test failed to reveal abnormality, however, the mutant mice showed prolonged sniffing to a stranger mouse. In a social novelty test, motopsin-deficient mice showed prolonged interest even in a familiar mouse. Consistent with such behavioral deficits, the spine density on apical dendrites of pyramidal neurons was significantly decreased at hippocampus CA1 region, which is known to be crucial for spatial memory and social behavior.
We have previously identified SEZ6 as a motopsin-binding protein. SEZ6 immunoreactivity (IR) was detected at the hippocampal CA1 region, cerebral cortex, lateral amygdala, and caudate putamen using anti-SEZ6 antibody, which was prepared against recombinant SEZ6 protein. It was noted that SEZ6 IR was obvious in the cerebral cortex at postnatal day (P) 7 and the CA1 hippocampus at P10, suggesting interaction with motopsin in these regions. Similar localization was observed in the human brain and spinal cord.
Our results suggest that motopsin secreted from neuronal cells anchors to SEZ6 proteins on neurons and that lack of motopsin function causes some symptom of mental retardation, eg, impaired memory formation and abnormal social behavior, through the defect of hippocampal function.
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